Recently, a team led by Dr. Liu Bao, Deputy Director of the Department of Vascular Surgery at PUMCH, in collaboration with researchers from BGI·Research in Beijing, published their findings in Nature Cardiovascular Research, a Nature Research journal. This study represents the first investigation into the mysterious plaque tertiary lymphoid organs (PTLOs) in patients with atherosclerosis, elucidating their characteristics, functions, and clinical implications. The research opens up new avenues for the prevention and treatment of cardiovascular diseases. The findings reveal that the presence of tertiary lymphoid organs (TLOs) is closely associated with the development of symptoms such as stroke, serving as an independent risk factor for symptomatic carotid stenosis. This paper was also the journal's cover story for the month. The study was supported by the National Natural Science Foundation of China, Beijing Natural Science Foundation, and the National High Level Hospital Clinical Research Funding, among others.

Atherosclerosis involves the formation of plaques through lipid deposition in blood vessel walls. Previous research has demonstrated that atherosclerotic plaques exhibit the characteristic of chronic inflammation, with macrophages, B cells, and smooth muscle cells being particularly active within plaques. However, the mechanisms underlying the development and progression of inflammation in arterial walls have remained a mystery.

To comprehensively analyze the cellular composition and spatial structure of atherosclerotic plaques, researchers examined samples from 149 patients with carotid plaques. Using single-cell RNA sequencing and spatial transcriptomics, they constructed a “cell atlas” of the plaques. Through systematic analysis, the team identified TLOs within human carotid atherosclerotic plaques for the first time.

Unlike primary lymphoid organs such as the thymus and bone marrow, or secondary lymphoid organs including the spleen and lymph nodes, TLOs are induced postnatally within non-lymphoid tissues. They are collections of large numbers of immune cells, including B cells and plasma cells, commonly observed in chronic inflammatory tissues associated with autoimmune diseases, chronic infections, and cancer.

The researchers observed that B cells within the TLOs in plaques differentiate into plasma cells and secrete IgG antibodies. When IgG antibodies activate macrophages to release inflammatory cytokines, plaques become unstable, increasing the risk of rupture.

Clinical statistical results are highly consistent with these research findings. Patients with PLTOs had a 3.5-fold higher risk of cerebrovascular events (such as stroke) compared to patients without these structures.

▲Close association between TLOs and clinical symptoms of carotid atherosclerosis

This study demonstrates for the first time TLOs as an independent risk factor for symptoms of carotid atherosclerosis, with the potential to become a novel indicator for predicting arterial plaque stability. The research suggests that developing targeted therapies against IgG antibodies to reduce their excessive secretion could enhance plaque stability.

The researchers also observed that fibroblast-like smooth muscle cells within plaques function to recruit B cells, indicating that inhibiting the molecular pathways of these cells could delay TLO formation. The B cells accumulated in TLOs derive not only from circulating blood but also partially from perivascular adipose tissue, providing a novel perspective for further exploring the relationship between obesity and atherosclerosis.

Dr. Liu Bao stated that continued advancement in TLO research may enable a transition from "passive treatment" to "active prevention", bringing new hope to hundreds of millions of atherosclerosis patients worldwide. Medical experts emphasize that for the general public, particularly high-risk populations including those with hypertension, diabetes, obesity, or smoking habits, regular health screenings (such as carotid ultrasound and lipid testing) are especially important. In addition, they need to change their lifestyle promptly, including reducing weight and sugar intake, and quitting smoking, to reduce abnormal proliferation of perivascular adipose tissue, decrease B cell accumulation, and lower plaque rupture risk. If symptoms of "mini-stroke" such as transient visual blurring or limb numbness occur, immediate medical attention should be sought.

Written by Gan Dingzhu and Chen Xiao

Pictures courtesy of the Department of Vascular Surgery

Edited by Gan Dingzhu and Chen Xiao

Chief Editor Duan Wenli

Supervised by Wu Peixin